To study the effect of ethanol and other drugs on folate metabolism, we will evaluate with microbiologic assays and radioassay the effect of standardized meals, short-term fasting, and short-term ingestion of ethanol on serum folate level, plasma cojugase activity, and urinary folate excretion in volunteers. Similarly, we will study the effect of diphenylhydantoin on folate balance in volunteers. Mechanisms by which these drugs impair folate metabolism will be sought be studies in the rat of biliary folate excretion by bile duct cannulation and hepatic folate metabolism by isolated liver perfusion. We will study by modifications of our radioassay the effect of certain drugs and diseases on serum levels of specific and nonspecific folate binders, and, with HeLa cells and marrow cultures, the effect of these binders on in vitro cellular transport of radiolabeled folates. Finally, we will study the prevalence and hematologic significance of folate deficiency in patients with sickle cell anemia.